Certain activated macrophages in close contact with target cells have been shown to be cytotoxic in vitro and in vivo. The requirements, conditions and mechanisms involved in macrophage to cell adhesion and cytotoxicity need to be further investigated. This information is relevant to the exploitation of macrophage cytotoxicity in the treatment of malignancy. The proposed work will examine the features of macrophage-to-cell adhesion and of macrophage cytotoxicity in vitro. In addition, a rather stringent model for macrophage cytotoxicity in vivo will be developed, in which tumor cells are transplanted to subcutaneous sites where macrophage rich exudates can be induced. In this model the host's macrophage system can be additionally stimulated by the administration of killed microorganisms, endotoxins or by delayed sensitivity reactions. BIBLIOGRAPHIC REFERENCES: M. Rabinovitch. Macrophage spreading in vitro, in R. van Furth (ed) Mononuclear Phagocytes in Immunity, Infection and Pathology, Blackwell Scientific Publications, Oxford, 1975, p.369-383. M. Rabinovitch and M.J. DeStefano. Cell to substrate adhesion and spreading: inhibition by cationic anesthetics. J. Cell Physiology 85: 189-193,1975.